This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mitochondria is an organelle that controls the life or death of a cell. It also provides most of the energy needs of a cells and is responsible for the metabolism of many important biomolecules. Previous studies have shown that mitochondria membrane potential is altered during malignant transformation of many types of cancers. Recent study of mitochondria dynamics also indicates a significant change in their shape, network and dynamic movement during various physiological and pathological process including carcinogenesis progression and stem cell differentiation. However, most of these observations are at optical microscopy resolution. The molecular events underlying these dynamics and transformation of the organelle are vaguely understood. This proposal is aimed to use cryo-ET to visualize and reconstruct the 3D fine structure of mitochondria at various levels of resolution in cells. Cell lines or primary cells in a series of stages in malignant transformation (i.e. normal, precancer, primary cancer and metastatic cancer) will be examined.